{"title":"Role of mitochondria in physiological activities, diseases, and therapy.","authors":"Lilin Wang, Xiaoting Zhou, Tianqi Lu","doi":"10.1186/s43556-025-00284-5","DOIUrl":"10.1186/s43556-025-00284-5","url":null,"abstract":"<p><p>Mitochondria are generally considered essential for life in eukaryotic organisms because they produce most of the energy or adenosine triphosphate (ATP) needed by the cell. Beyond energy production, it is now widely accepted that mitochondria also play a pivotal role in maintaining cellular homeostasis and signaling. The two core processes of mitochondrial dynamics, fission and fusion, serve as crucial foundations for maintaining mitochondrial morphology, distribution, and quantity, thereby ensuring cellular homeostasis. Mitochondrial autophagy (mitophagy) ensures the selective degradation of damaged mitochondria, maintaining quality control. Mitochondrial transport and communication further enhance their role in cellular processes. In addition, mitochondria are susceptible to damage, resulting in dysfunction and disruption of intracellular homeostasis, which is closely associated with the development of numerous diseases. These include mitochondrial diseases, neurodegenerative diseases, cardiovascular diseases (CVDs) and stroke, metabolic disorders such as diabetes mellitus, cancer, infectious diseases, and the aging process. Given the central role of mitochondria in disease pathology, there is a growing need to understand their mechanisms and develop targeted therapies. This review aims to provide a comprehensive overview of mitochondrial structure and functions, with a particular focus on their roles in disease development and the current therapeutic strategies targeting mitochondria. These strategies include mitochondrial-targeted antioxidants, modulation of mitochondrial dynamics and quality control, mitochondrial genome editing and genetic therapy, and mitochondrial transplantation. We also discuss the challenges currently facing mitochondrial research and highlight potential future directions for development. By summarizing the latest advancements and addressing gaps in knowledge, this review seeks to guide future research and clinical efforts in the field of mitochondrial medicine.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"42"},"PeriodicalIF":6.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shiyuan Huang, Fang Yan, Yi Qiu, Tao Liu, Wenjin Zhang, Yige Yang, Rao Zhong, Yang Yang, Xi Peng
{"title":"Exosomes in inflammation and cancer: from bench to bedside applications.","authors":"Shiyuan Huang, Fang Yan, Yi Qiu, Tao Liu, Wenjin Zhang, Yige Yang, Rao Zhong, Yang Yang, Xi Peng","doi":"10.1186/s43556-025-00280-9","DOIUrl":"10.1186/s43556-025-00280-9","url":null,"abstract":"<p><p>Exosomes, lipid bilayer nanovesicles secreted by nearly all cell types, play pivotal roles in intercellular communication by transferring proteins, nucleic acids, and lipids. This review comprehensively summarizes their multiple functions in inflammation and cancer. In inflammation, exosomes exhibit context-dependent pro- or anti-inflammatory effects: they promote acute responses by delivering cytokines and miRNAs to activate immune cells, yet suppress chronic inflammation via immunoregulatory molecules. Two representative inflammatory diseases, namely sepsis and inflammatory bowel disease, were highlighted to elucidate their roles in the acute and chronic inflammatory diseases. In cancer, exosomes orchestrate tumor microenvironment (TME) remodeling by facilitating angiogenesis, metastasis, and immune evasion through interactions with cancer-associated fibroblasts, tumor-associated macrophages, and extracellular matrix components. Furthermore, exosomes can facilitate the transition from inflammation to cancer by impacting pertinent signaling pathways via their transported oncogenic and inflammatory molecules. Tumor-derived exosomes also serve as non-invasive biomarkers correlating with disease progression. Clinically, exosomes demonstrate promise as therapeutic agents and drug carriers, evidenced by ongoing trials targeting inflammatory diseases and cancers. However, challenges in isolation standardization, scalable production, and understanding functional heterogeneity hinder clinical translation. Future research should prioritize elucidating cargo-specific mechanisms, optimizing engineering strategies, and advancing personalized exosome-based therapies. By bridging molecular insights with clinical applications, exosomes hold great potential in precision medicine for inflammation and oncology.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"41"},"PeriodicalIF":6.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Soon Chul Heo, In-Hye Nam, Bo Ram Keum, Yeo Gyun Yun, Jae-Yeol Lee, Hyung Joon Kim
{"title":"C-X-C motif chemokine ligand 1 derived from oral squamous cell carcinoma promotes cancer-associated fibroblast differentiation and tumor growth.","authors":"Soon Chul Heo, In-Hye Nam, Bo Ram Keum, Yeo Gyun Yun, Jae-Yeol Lee, Hyung Joon Kim","doi":"10.1186/s43556-025-00281-8","DOIUrl":"10.1186/s43556-025-00281-8","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs), the predominant stromal cells in the tumor microenvironment (TME), play a critical role in the progression of solid tumors, including oral squamous cell carcinoma (OSCC). However, the molecular mechanisms by which OSCC-derived factors mediate CAF differentiation remain incompletely understood. This study investigates the role of the C-X-C motif chemokine ligand 1 (CXCL1), secreted by OSCC cells, in promoting CAF differentiation and its downstream impact on tumor progression. Gingival fibroblasts (GFs) were treated with conditioned medium (CM) from various OSCC cell lines to assess their potential to induce CAF differentiation. Proteomic analysis using liquid chromatography-mass spectrometry identified CXCL1 as a key factor highly secreted in SCC25-derived CM, which exhibited the strongest capacity to induce CAF differentiation. CXCL1 synergistically enhanced TGF-β1-induced differentiation of GFs into α-smooth muscle actin (αSMA)- and vimentin-expressing CAFs by approximately 1.5-fold, confirming its co-stimulatory function. Conversely, silencing its receptor CXCR2 reduced CAF marker expression by over 50%, indicating a strong inhibitory effect on CAF differentiation. In vivo, co-injection of SCC25 cells with GFs significantly promoted tumor growth and stromal CAF marker expression, whereas CXCR2 knockdown in GFs led to a ~ 40% reduction in tumor volume and reduced αSMA/vimentin-positive CAFs. These findings establish CXCL1 as a pivotal mediator of CAF differentiation through CXCR2-dependent signaling, and highlight that the CXCL1-CXCR2 axis is a promising therapeutic target for modulating stromal-tumor interactions in OSCC.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"40"},"PeriodicalIF":6.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Histone and non-histone lactylation: molecular mechanisms, biological functions, diseases, and therapeutic targets.","authors":"Xia Peng, Juan Du","doi":"10.1186/s43556-025-00275-6","DOIUrl":"10.1186/s43556-025-00275-6","url":null,"abstract":"<p><p>Lysine lactylation (Kla) is a recently discovered post‑translational modification in which a lactyl moiety is transferred onto the ε‑amino group of lysine residues, linking cellular metabolism to epigenetic and signaling pathways. This process is regulated by a range of enzymes and metabolites, including lactate, \"lactyltransferases (writers)\", \"Delactylases (erasers)\", and \"readers\" involved in the modification. Histone lactylation has been observed in H2A, H2B, H3, and H4, with H3K18la and H4K12la being the most extensively studied sites, linked to numerous biological functions. Beyond chromatin, Kla has also been identified in a growing number of non-histone proteins, further expanding its functional significance. For instance, non-histone proteins such as AARS1-K120la, ACSS2-Kla, MRE11-K673la, NBS1-K388la and GNAT13-Kla has illuminated novel regulatory mechanisms and reinforced the potential of non-histone Kla as a promising avenue for research. Importantly, aberrant Kla patterns have been linked to various disease states, including cancer, inflammation, and metabolic disorders, highlighting its emerging potential as a biomarker and therapeutic target. In this review, we systematically summarize the molecular mechanisms, biological functions, disease associations, and therapeutic implications of both histone and non-histone Kla. By integrating current findings and discussing existing challenges, we aim to provide a comprehensive overview that will deepen understanding of Kla biology and inspire future research into its diagnostic and therapeutic potential.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"38"},"PeriodicalIF":6.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yaohua Cai, Wenyi Lin, Jun Deng, Zhipeng Cheng, Yanyi Tao, Hui Lu, Yunqing Xia, Tingting Wu, Liang V Tang, Yu Hu
{"title":"Application of multigene panel testing for bleeding, thrombotic, and platelet disorders in patients and the general population in China.","authors":"Yaohua Cai, Wenyi Lin, Jun Deng, Zhipeng Cheng, Yanyi Tao, Hui Lu, Yunqing Xia, Tingting Wu, Liang V Tang, Yu Hu","doi":"10.1186/s43556-025-00283-6","DOIUrl":"10.1186/s43556-025-00283-6","url":null,"abstract":"<p><p>Bleeding, thrombotic, and platelet disorders (BTPDs) are rare but complex conditions with diverse clinical presentations that often delay accurate diagnosis. In this study, we developed an Expanded Thrombohemostasis (ExTH) gene panel comprising 130 diagnostic and risk-associated genes. This panel was applied to 747 patients and 760 controls, representing the largest genetic screening study for BTPDs in an Asian population to date. A high overall diagnostic yield of 54.8% was achieved, with mutation carriers exhibiting more severe clinical phenotypes. Notably, the diagnostic rate was significantly higher in younger individuals, underscoring the clinical value of early genetic screening. Beyond traditional Tier 1 gene panels, we identified disease-causing variants in unexpected categories in 4.28% of patients, revealing extensive genotype-phenotype overlap and advocating for a broader diagnostic approach. Some pathogenic variants exhibited normal results in conventional coagulation assays, highlighting the limitations of standard functional testing in detecting underlying genetic causes. These findings establish the ExTH gene panel as a powerful tool for comprehensive genetic diagnosis, capable of capturing clinically relevant variants that would be missed by conventional approaches. This study provides new insight into the molecular landscape of BTPDs, and supports the integration of broad gene panel testing into routine clinical workflows to improve diagnostic accuracy, risk stratification, and personalized treatment.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"39"},"PeriodicalIF":6.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The EZH2 selective inhibitor ZLD1039 attenuates UUO-induced renal fibrosis by suppressing YAP activation.","authors":"Qingling Xia, Fujiang Xu, Lidan Zhang, Wenfei Ding, Jiang Liu, Jing Liu, Minhao Chen, Santao Ou, Yong Xu, Li Wen","doi":"10.1186/s43556-025-00276-5","DOIUrl":"10.1186/s43556-025-00276-5","url":null,"abstract":"<p><p>Renal fibrosis is a manifestation of the progression of chronic kidney disease (CKD) and chronic inflammation is a main driver in the development of renal fibrosis. Yes-associated protein (YAP), acting as a transcriptional co-activator within the Hippo signaling pathway, has been implicated in renal fibrosis. Enhancer of zeste homolog 2 (EZH2) exhibits high expression level in renal fibrosis induced by unilateral ureteral obstruction (UUO), yet the interplay between YAP and EZH2 in renal fibrosis remains to be elucidated. ZLD1039, a selective inhibitor of EZH2, has demonstrated protective effects against cancer and acute kidney injury (AKI). In this study, we conducted a systemic pharmacological investigation to determine if ZLD1039 treatment mitigates UUO-induced renal inflammation and fibrosis through modulation of the Hippo-YAP pathway. Our results revealed that UUO triggered renal inflammation and collagen deposition, with significant activation of YAP. Notably, ZLD1039 treatment effectively alleviated renal inflammation and fibrosis, while inhibiting the expression and nuclear translocation of YAP. Mechanically, we observed a notable down-regulation of large tumor suppressor homolog 1 (LATS1) in parallel with the up-regulation of EZH2. Furthermore, inhibition of EZH2 by ZLD1039 was linked to the up-regulation of LATS1 expression and YAP inactivation. Similarly, in vitro pharmacological inhibition of EZH2 by ZLD1039 resulted in elevated LATS1 expression and diminished YAP activation. Collectively, our findings suggest that ZLD1039, a selective inhibitor of EZH2, likely attenuates renal inflammation and fibrosis probably by up-regulating LATS1 and inhibiting YAP activation. This mechanistic link between EZH2 and YAP provides a fresh perspective on treating renal fibrosis.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"36"},"PeriodicalIF":6.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting Mutant Protein Kinase B with Lysine-Selective Salicylaldehyde Inhibitors and Zn<sup>2</sup>⁺ Chelation: A Novel Therapeutic Strategy.","authors":"Runpeng Yu, Yiran Wu, Long Zhang","doi":"10.1186/s43556-025-00278-3","DOIUrl":"10.1186/s43556-025-00278-3","url":null,"abstract":"","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"37"},"PeriodicalIF":6.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Qiao, Lv Zhou, Jianyu Nie, Jinshui Li, Yangchun Hu, Peng Gao, Bingshan Wu, Hongwei Cheng, Xingliang Dai
{"title":"Transmembrane emp24 domain-containing protein 3 promotes the malignant progression of glioma by regulating the ZBTB7A signaling axis.","authors":"Yang Qiao, Lv Zhou, Jianyu Nie, Jinshui Li, Yangchun Hu, Peng Gao, Bingshan Wu, Hongwei Cheng, Xingliang Dai","doi":"10.1186/s43556-025-00274-7","DOIUrl":"10.1186/s43556-025-00274-7","url":null,"abstract":"<p><p>Glioblastoma (GBM) is highly malignant with a poor prognosis. Exploring new therapeutic targets in GBM is an effective strategy for the prognosis of GBM patients. The Transmembrane emp24 domain-containing protein 3 (TMED3) gene has been found to play a role in the development of various cancers, but its mechanism in GBM remains unclear. This study combined the TCGA database, single-cell RNA sequencing, and in vitro and in vivo experiments to systematically investigate the role of TMED3 in GBM and its potential mechanisms. The study found that the TMED3 gene is differentially expressed in GBM samples, and high expression is associated with a higher grade of GBM and a poorer prognosis. In vitro and in vivo experiments confirmed that the upregulation of TMED3 promoted GBM proliferation, invasion, and migration. Further immunoprecipitation and functional rescue experiments revealed that Zinc finger and BTB domain-containing protein 7A (ZBTB7A) acts as a downstream target of TMED3. TMED3 promotes the malignant progression of GBM by regulating ZBTB7A. In conclusion, this study reveals that TMED3 promotes GBM development through the regulation of the ZBTB7A signaling axis, providing new insights for targeted therapy of GBM.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"35"},"PeriodicalIF":6.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Wang, Huanhui Wang, Jing Tan, Zhijie Cao, Qun Wang, Hongkun Wang, Shouwei Yue, Wei Li, Dong Wang
{"title":"Therapeutic effect of mesenchymal stem cells and their derived exosomes in diseases.","authors":"Yang Wang, Huanhui Wang, Jing Tan, Zhijie Cao, Qun Wang, Hongkun Wang, Shouwei Yue, Wei Li, Dong Wang","doi":"10.1186/s43556-025-00277-4","DOIUrl":"10.1186/s43556-025-00277-4","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are multipotent stem cells characterized by their robust proliferative capacity, homing ability, differentiation potential, and low immunogenicity in vitro. MSCs can be isolated from a variety of tissues, primarily including but not limited to bone marrow, adipose tissue, umbilical cord, placenta, and dental pulp. Although there have been a large number of clinical studies on the treatment of diseases by MSCs and MSCs-derived exosomes (MSCs-EXO), the large-scale clinical application of MSCs and MSCs-EXO have been limited due to the heterogeneity of the results among various studies. This review provides a detailed description of the classification and characterization of MSCs and MSCs-EXO, as well as their extraction methods. Furthermore, this review elaborates on three key mechanisms of MSCs and MSCs-EXO: paracrine mechanisms, immunomodulatory and anti-inflammatory effects, as well as their promotion of tissue regeneration. This review also examines the role of MSCs and MSCs-EXO in cardiovascular diseases, neurological disorders, autoimmune diseases, musculoskeletal disorders, and other systemic diseases over the past five years, while discussing the challenges and difficulties associated with their clinical application. Finally, we systematically summarized and analyzed the potential causes of the various heterogeneous results currently observed. Additionally, we provided an in-depth discussion on the challenges and opportunities associated with the clinical translation of disease treatment approaches based on MSCs, MSCs-EXO, and engineered exosomes.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"34"},"PeriodicalIF":6.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}